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The comet assay is a versatile method to detect nuclear DNA damage in individual eukaryotic cells, from yeast to human. The types of damage detected encompass DNA strand breaks and alkali-labile sites (e.g., apurinic/apyrimidinic sites), alkylated and oxidized nucleobases, DNA-DNA crosslinks, UV-induced cyclobutane pyrimidine dimers and some chemically induced DNA adducts. Depending on the specimen type, there are important modifications to the comet assay protocol to avoid the formation of additional DNA damage during the processing of samples and to ensure sufficient sensitivity to detect differences in damage levels between sample groups. Various applications of the comet assay have been validated by research groups in academia, industry and regulatory agencies, and its strengths are highlighted by the adoption of the comet assay as an in vivo test for genotoxicity in animal organs by the Organisation for Economic Co-operation and Development. The present document includes a series of consensus protocols that describe the application of the comet assay to a wide variety of cell types, species and types of DNA damage, thereby demonstrating its versatility.The comet assay is commonly used to assess DNA damage. This collection of consensus protocols includes adaptations for a wide range of species and sample types, assay formats and detection of different types of DNA lesions.

Background and Objective: Cell damage caused by oxidative stress is one of the mechanisms that has been implicated for a long time in various neurodegenerative disorders such as Parkinson's and Alzheimer's diseases. Lavandula stoechas has been used in European-Iranian traditional medicine for the treatment of various diseases, primarily cardiovascular and neurodegenerative disorders. In this study, the neuroprotective effects of Lavandula stoechas L extracts against H2O2 toxicity in SH-SY5Y cells were investigated in vitro. Materials and Methods: Several extracts were prepared from the flowering branches of the L. stoechas. The neuroprotective activity of the extracts against H2O2 damage in SH-SY5Y cells and their effects on apoptotic processes were evaluated based on cell viability against H2O2 toxicity, colony formation capacity and effect on apoptotic protein levels. Results: It was determined that pretreatment with 1-10 ppm doses of L. stoechas extracts (2-24 hrs) had a significant protective effect against 250 mu M H2O2 toxicity. It was shown for the first time that L. stoechas extracts exhibited a significant protective effect for colony formation at 1-10 ppm doses and protected the colony numbers by 50% against H2O2 toxicity. In addition, it was determined that they were able to exert anti-apoptotic effects by decreasing Bax levels and increasing Bcl-2, thereby decreasing the Bax/Bcl-2 protein ratio. Conclusion: In this study, neuroprotective activities of different L. stoechas extracts were compared for the first time. Total methanol, ethyl acetate and water (infusion) extracts have shown potent neuroprotective effects and the cellular processes underlying its effects have been proven by these preliminary data.

BACKGROUND Oilseed rape requires sulfur (S) fertilization. Cadmium (Cd) differs dramatically in agricultural soils. Rice-oilseed rape rotation distributes widely and contributes the majority of rapeseeds in Asian countries. It was reported that S metabolism was involved in Cd uptake in seedlings of oilseed rape, although the effects of S on Cd accumulation and seed yield at maturity are still unclear. RESULTS We performed a pot experiment including two Cd rates (0.35 and 10.35 mg kg(-1), as low and high Cd soil) and four S levels (0, 30, 60 and 120 mg kg(-1)). The results showed that low S application (30 mg kg(-1)) resulted in two-fold higher seed-Cd concentration irrespective of soil Cd levels. The responsible mechanism might be that Cd translocation into rapeseeds was involved in sulfate transporters, which could be strongly expressed in shoots and roots when supplying sulfate under S-starvation conditions, but depressed under a S-sufficient environment. For high Cd soil, seed yield decreased by 36%, 48% and 72% at 30, 60 and 120 mg S kg(-1) compared to non-S treatment, whereas there were no differences for low Cd soil. Antagonistic effects of S and Cd existed for seed yield according to structure equation model analysis. CONCLUSION Oilseed rape can be grown in low-Cd fields as a safe food crop with high levels of sulfur fertilizers (>60 mg S kg(-1)). In high-Cd fields, oilseed rape is recommended as a Cd-remediation crop, and rapeseeds should only be used for industrial purposes and not for food. (c) 2021 Society of Chemical Industry.

Astrocytes are greatly impacted by oxidative stress, which can also be related to neurodegenerative diseases. Therefore, preventing the production of reactive oxygen species (ROS) is crucial for maintaining healthy cells. Large conductance Ca2+-activated big potassium (BK) channel openers are effective in eliminating the effects of oxidative stress. The present study aims to determine if NS11021, a BK channel opener, protects the astrocytcs from harmful effects of hydrogen peroxide (H2O2), which is an oxidative stress inducer. For this purpose, primary astrocyte cultures were incubated with H2O2, NS11021, and Iberiotoxin both separately and together. H2O2 decreased cell viability by approximately 50% and increased the number of ROS-positive astrocytes. However, NS11021, but not Iberiotoxin, reversed the deleterious effects of H2O2 on cell viability and decreased ROS production. Moreover, dysregulations in Cyclin D1/CDK6/p21 gene expressions under conditions of oxidative stress were regulated again by the opener. To the best of our knowledge, this study has been the first to reveal that NS11021 reversed the deleterious effects of H2O2 on cell viability by regulating ROS production in astrocytcs. Its effect may also be related to the regulation of cell cycle at the transcriptional level. NS11021 may also be used as an agent for the treatment of oxidative-stress related dysfunction of astrocytes.

Diabetes, mobile phone use, and obesity have increased simultaneously in recent years. The radiofrequency radiation (RFR) emitted from mobile phones is largely absorbed in the heads of users. With 5 G, which has started to be used in some countries without the necessary precautions being taken, the amount of RFR to which living things are exposed will increase. In this study, the changes in energy homeostasis and redox balance caused by 5 G (3.5 GHz, GSM-modulated) were explored. The effects of RFR on the brains of diabetic and healthy rats were investigated and histopathological analysis was performed. Twenty-eight Wistar albino rats weighing 200-250 g were divided into 4 groups as sham, RFR, diabetes, and RFR+diabetes groups (n = 7). The rats in each group were kept in a plexiglass carousel for 2 h a day for 30 days. While the rats in the experimental groups were exposed to RFR for 2 h a day, the rats in the sham group were kept under the same experimental conditions but with the radiofrequency generator turned off. At the end of the experiment, brain tissues were collected from euthanized rats. Total antioxidant (TAS), total oxidant (TOS), hydrogen peroxide (H2O2), ghrelin, nesfatin-1, and irisin levels were determined. In addition, histopathological analyses of the brain tissues were performed. The specific absorption rate in the gray matter of the brain was calculated as 323 mW/kg and 195 mW/kg for 1 g and 10 g averaging, respectively. After RFR exposure among diabetic and healthy rats, decreased TAS levels and increased TOS and H2O2 levels were observed in brain tissues. RFR caused increases in ghrelin and irisin and a decrease in nesfatin-1 in the brain. It was also observed that RFR increased the number of degenerated neurons in the hippocampus. Our results indicate that 3.5 GHz RFR causes changes in the energy metabolism and appetite of both healthy and diabetic rats. Thus, 5 G may not be innocent in terms of its biological effects, especially in the presence of diabetes., Van Yuzuncu Yil University Scientific Research Foundation (BAP, Turkey); [TYD-2021-9598], This work was supported by Van Yuzuncu Yil University Scientific Research Foundation (BAP, Turkey, grant number: TYD-2021-9598) . The authors would like to thank Dr. Mustafa Cakir and Yusuf Emir Bektas ? for their valuable contribution.

Taurine (2-aminoethanesulfonic acid) is required for ensuring proper muscle functioning. Knockout of the taurine transporter in mice results in low taurine concentrations in the muscle and associates with myofiber necrosis and diminished exercise capacity. Interestingly, regulation of taurine and its transporter is altered in the mdx mouse, a model for Duchenne Muscular Dystrophy (DMD). DMD is a genetic disorder characterized by progressive muscle degeneration and weakness due to the absence of dystrophin from the muscle membrane, causing destabilization and contraction-induced muscle cell damage. This review explores the physiological role of taurine in skeletal muscle and the consequences of a disturbed balance in DMD. Its potential as a supportive treatment for DMD is also discussed. In addition to genetic correction, that is currently under development as a curative treatment, taurine supplementation has the potential to reduce muscle inflammation and improve muscle strength in patients.

Selenium (Se) is found in plants both in inorganic and organic forms as selenoamino acids and methylated complexes. Se influences growth and physiological parameters, viz. root and shoot growth, starch accumulation, water status regulation, respiration, germination promotion, nitrogen assimilation and delaying senescence in plants. Se deficiency causes many human medical conditions, viz. cancer, liver disease, cardiovascular disease, thyroid disease, Keshan disease and central nervous system disorders. Plants need Se to alleviate abiotic stresses, viz. high/low temperatures, drought, salinity, light, UV-B radiation and toxic metals/metalloids. Ameliorative role of Se, applied in relatively low doses, against abiotic stresses was mediated via enzymatic and non-enzymatic antioxidation. Chemical form, application method, edaphic presence and bioavailability of Se and its interaction with other elements regulate Se biofortification and abiotic stress tolerance in food and medicinal crops. Popular scientific search engines, viz. PubMed, Pubget, ScienceDirect, Medline, Scopus, SpringerLink, Mendeley, EMBASE, Google Scholar and JSTOR were searched to retrieve published articles by using pre-determined search strings involving selenium, plants, stress, metals, metalloids, etc. The retrieved literature encompasses the role of Se biofortification in enhancing dietary Se in crops and its bioavailability. The review also presents recent trends in Se-mediated amelioration of toxic metal and metalloid stresses via maintaining cell membrane integrity, functioning of photosynthetic machinery, inhibition against uptake and translocation of toxic metals and metalloids, control over the uptake and distribution of mineral nutrition and conversion of toxic metals and metalloids to non-toxic Se-metal complexes. Furthermore, current research on the genetic engineering and omics studies on Se biofortification and Se-mediated abiotic stress tolerance are also discussed. The present review comprehensively elucidates the beneficial role Se biofortification in developing resilience in crops against toxic metals and metalloids. Presidency University, India This work was supported by the Faculty Research and Professional Development Fund (FRPDF), a financial assistance from Presidency University, India.

Iron plays a crucial role in many physiological processes of the human body, but iron is continuously deposited in the brain as we age. Early studies found iron overload is directly proportional to cognitive decline in Alzheimer’s disease (AD). Amyloid precursor protein (APP) and tau protein, both of which are related to the AD pathogenesis, are associated with brain iron metabolism. A variety of iron metabolism-related proteins have been found to be abnormally expressed in the brains of AD patients and mouse models, resulting in iron deposition and promoting AD progression. Amyloid β (Aβ) and hyperphosphorylated tau, two pathological hallmarks of AD, can also promote iron deposition in the brain, forming a vicious cycle of AD development-iron deposition. Iron deposition and the subsequent ferroptosis has been found to be a potential mechanism underlying neuronal loss in many neurodegenerative diseases. Iron chelators, antioxidants and hepcidin were found useful for treating AD, which represents an important direction for AD treatment research and drug development in the future. The review explored the deep connection between iron dysregulation and AD pathogenesis, discussed the potential of new hypothesis related to iron dyshomeostasis and ferroptosis, and summarized the therapeutics capable of targeting iron, with the expectation to draw more attention of iron dysregulation and corresponding drug development.

Background Cd accumulation in plant cells results in dramatic problems including oxidative stress and inhibition of vital enzymes. It also affects mineral uptakes by disrupting membrane permeability. Interaction among Cd and other plant nutrient elements changes the nutritional contents of crops and reduces their yield. Methods and results In the present study, Cd stress in Brachypodium distachyon led to the upregulation of some heavy metal transport genes (influx or efflux) encoding cation-efflux proteins, heavy metal-associated proteins and NRAMP proteins. The Arabidopsis orthologs of the differentially expressed B. distachyon genes (DEGs) under Cd toxicity were identified, which exhibited Bradi4g26905 was an ortholog of AtALY1-2. Detailed co-expression network and gene ontology analyses found the potential involvement of the mRNA surveillance pathway in Cd tolerance in B. distachyon. These genes were shown to be downregulated by sulfur (S) deficiency. Conclusions This is the first transcriptomic study investigating the effect of Cd toxicity in B. distachyon, a model plant for genomic studies in Poaceae (Gramineae) species. The results are expected to provide valuable information for more comprehensive research related to heavy metal toxicity in plants. Akdeniz University Scientific Research Projects Coordination UnitAkdeniz University [FBA-2018-3532] The study was funded by Akdeniz University Scientific Research Projects Coordination Unit. Grant number: FBA-2018-3532. WOS:000721666100001 PubMed: 34812999

Objectives To investigate the possible protective effects of resveratrol against oxidative testicular damage due to scattered radiation during pelvic ionizing radiation exposure in rats. Methods Rats were divided into 5 groups; control, radiation, and radiation + resveratrol therapy in early and late periods. Under anesthesia, 20 Gy ionizing radiation was applied to prostatic region. Resveratrol was administered (10 mg/kg/day) orally before ionizing radiation exposure. Animals were decapitated at the end of 1st and 10th weeks. Biochemical markers of oxidative stress; caspase-3 and sirtuin-1 protein expressions; testosterone levels were evaluated, histological examinations were performed. Results Significant increases in malondialdehyde, 8-hydroxy-deoxyguanosine levels, myeloperoxidase, and caspase-3 activities were observed after ionizing radiation exposure, also superoxide dismutase and glutathione activities were significantly decreased. Radiotherapy increased caspase-3 and decreased sirtuin-1 protein expressions. Resveratrol treatment significantly reversed these parameters and also reversed the decrease in testosterone levels back to control levels in late period. Conclusion Resveratrol showed antioxidant and sirtuin-activating properties against oxidative damage caused by scattered radiation to testis and provided hormonal protection. These results suggest that resveratrol may be an alternative protective agent on testicular tissues against the effects of scattered pelvic radiation.

Microglia play a crucial role in the inflammatory brain response to infection. However, overactivation of microglia is neurotoxic. Toll-like receptor 4 (TLR4) is involved in microglial activation via lipopolysaccharide (LPS), which triggers a variety of cytotoxic pro-inflammatory markers that produce deleterious effects on neuronal cells. Ferulic acid (FA) is a phenolic compound that exerts antioxidant and anti-inflammatory effects in neurodegenerative disease. However, the manner in which FA inhibits neuroinflammation-induced neurodegeneration is poorly understood. Therefore, we investigated the anti-inflammatory effects of FA against LPS-induced neuroinflammation in the mouse brain. First, we provide evidence that FA interferes with TLR4 interaction sites, which are required for the activation of microglia-induced neuroinflammation, and further examined the potential mechanism of its neuroprotective effects in the mouse hippocampus using molecular docking simulation and immunoblot analysis. Our results indicated that FA treatment inhibited glial cell activation, p-JNK, p-NFKB, and downstream signaling molecules, such as iNOS, COX-2, TNF-, and IL-1, in the mouse hippocampus and BV2 microglial cells. FA treatment strongly inhibited mitochondrial apoptotic signaling molecules, such as Bax, cytochrome C, caspase-3, and PARP-1, and reversed deregulated synaptic proteins, including PSD-95, synaptophysin, SNAP-25, and SNAP-23, and synaptic dysfunction in LPS-treated mice. These findings demonstrated that FA treatment interfered with the TLR4/MD2 complex binding site, which is crucial for evoking neuroinflammation via microglia activation and inhibited NFKB likely via a JNK-dependent mechanism, which suggests a therapeutic implication for neuroinflammation-induced neurodegeneration.

Edible flowers are attracting special therapeutic attention and their administration is on the rise. Edible flowers play pivotal modulatory roles on oxidative stress and related interconnected apoptotic/inflammatory pathways toward the treatment of cancer. In this review, we highlighted the phytochemical content and therapeutic applications of edible flowers, as well as their modulatory potential on the oxidative stress pathways and apoptotic/inflammatory mediators, resulting in anticancer effects. Edible flowers are promising sources of phytochemicals (e.g., phenolic compounds, carotenoids, terpenoids) with several therapeutic effects. They possess anti-inflammatory, anti-diabetic, anti-microbial, anti-depressant, anxiolytic, anti-obesity, cardioprotective, and neuroprotective effects. Edible flowers potentially modulate oxidative stress by targeting erythroid nuclear transcription factor-2/extracellular signal-regulated kinase/mitogen-activated protein kinase (Nrf2/ERK/MAPK), reactive oxygen species (ROS), nitric oxide (NO), malondialdehyde (MDA) and antioxidant response elements (AREs). As the interconnected pathways to oxidative stress, inflammatory mediators, including tumor necrosis factor (TNF)-alpha, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B), interleukins (ILs) as well as apoptotic pathways such as Bcl-2-associated X protein (Bax), Bcl-2, caspase and cytochrome C are critical targets of edible flowers in combating cancer. In this regard, edible flowers could play promising anticancer effects by targeting oxidative stress and downstream dysregulated pathways.

Melatonin has been reported to induce effective reduction in growth and development in a variety of tumors, including breast cancer. In triple-negative breast cancer (TNBC) cells, melatonin attenuates a variety of cancer features, such as tumor growth and apoptosis resistance, through a number of still poorly characterized mechanisms. One biological process that is important for TNBC cells is store-operated Ca2+ entry (SOCE), which is modulated by TRPC6 expression and function. We wondered whether melatonin might intersect with this pathway as part of its anticancer activity. We show that melatonin, in the nanomolar range, significantly attenuates TNBC MDA-MB-231 cell viability, proliferation, and migration in a time- and concentration-dependent manner, without having any effect on nontumoral breast epithelial MCF10A cells. Pretreatment with different concentrations of melatonin significantly reduced SOCE in MDA-MB-231 cells without altering Ca2+ release from the intracellular stores. By contrast, SOCE in MCF10A cells was unaffected by melatonin. In the TNBC MDA-MB-468 cell line, melatonin not only attenuated viability, migration, and SOCE, but also reduced TRPC6 expression in a time- and concentration-dependent manner, without altering expression or function of the Ca2+ channel Orai1. The expression of exogenous TRPC6 overcame the effect of melatonin on SOCE and cell proliferation, and silencing or inhibition of TRPC6 impaired the inhibitory effect of melatonin on SOCE. These findings indicate that TRPC6 downregulation might be involved in melatonin's inhibitory effects on Ca2+ influx and the maintenance of cancer hallmarks and point toward a novel antitumoral mechanism of melatonin in TNBC cells., Supported by MICINN (Grants BFU2016-74932-C2-1-P, BFU2016-74932-C2-2-P, PID2019-104084GB-C21 and PID2019-104084GB-C22) and Junta de Extremadura-Fondo Europeo de Desarrollo Regional (Grants IB16046 and GR18061). S. A., R. D.-B., and I. J. (contract TA18054) are supported by contracts from Junta de Extremadura-FEDER. D. F. is supported by Jordi Soler grant from CIBERCV (ISCIII, Madrid).

Drought, heat, and salinity, as well as pests, are stressing agents, which have impressively declined the productivity and quality of sugarcane crop in harsh environments. Our study aimed to examine the effect of various chemical ripeners as alternatives to enhancing the reactiveness of the enzymatic antioxidant system of sugarcane crop. The field experiment consisted of spraying the ingredients, ethephon, ethyl-trinexapac, glyphosate, carboxylic compounds (MTD) and methyl-sulfumeturon on the Brazilian commercial varieties, SP80-1842 and SP80-3280, before flowering stage. The enzymatic assay comprised the monitoring of the rate of degradation of free radical by ascorbate peroxidase (APX), catalase (CAT), peroxidase (POD) and superoxide dismutase (SOD) in the extract from leaves of 11-month-old plants. Spraying glyphosate at 0.15 L ha&minus, 1 with MTD at 1.00 L ha&minus, 1 provided the highest activity of CAT, 0.65 &micro, mol H2O2 min&minus, 1 mg&minus, 1 protein, in variety SP80-1842 Spraying glyphosate at 0.15 L ha&minus, 1 with ethephon at 0.33 L ha&minus, 1 caused the highest activity of APX, 1.70 nmol ascorbate min&minus, 1 protein, in variety SP80-3280. The conclusion is, therefore, that mixtures of glyphosate with the insecticide/acaricide, MTD, and with the synthetic ethylene-releasing product, ethephon could help sugarcane crop grow adequately under uncontrollable or unpredictable agroecosystems like marginal lands.

Place: Amsterdam Publisher: Elsevier WOS:000509631400010; International audience; Mangroves are tidal wetlands that are often under strong anthropogenic pressures, despite the numerous ecosystem services they provide. Pollution from urban runoffs is one such threats, yet some mangroves are used as a bioremediation tool for wastewater (WW) treatment. This practice can impact mangrove crabs, which are key engineer species of the ecosystem. Using an experimental area with controlled WW releases, this study aimed to determine from an ecological and ecotoxicological perspective, the effects of WW on the red mangrove crab Neosarmatium africanum. Burrow density and salinity levels (used as a proxy of WW dispersion) were recorded, and a 3-week caging experiment was performed. Hemolymph osmolality, gill Na+/K+-ATPase (NKA) activity and gill redox balance were assessed in anterior and posterior gills of N. africanum. Burrow density decreased according to salinity decreases around the discharged area. Crabs from the impacted area had a lower osmoregulatory capacity despite gill NKA activity remaining undisturbed. The decrease of the superoxide dismutase activity indicates changes in redox metabolism. However, both catalase activity and oxidative damage remained unchanged in both areas but were higher in posterior gills. These results indicate that WW release may induce osmoregulatory and redox imbalances, potentially explaining the decrease in crab density. Based on these results we conclude that WW release should be carefully monitored as crabs are key players involved in the bioremediation process.

Purpose The aim of this study is to determine the therapeutic effects of boric acid cell proliferation, invasion, migration, colony formation, cell cycle and apoptosis mechanisms in ovarian cancer cell line under in vitro conditions. Methods MDAH-2774 ovarian cancer cells were employed. Real-time PCR test was used to investigate changes in genes and proteins of cell cycle and apoptosis and identified miRNAs under the addition of boric acid. The apoptosis rates were calculated by TUNEL assay. Matrigel invasion, colony formation and Wound healing tests were used to determine invasion and migration. Oxidative stress index value was calculated for oxidative stress. Results Boric acid inhibited cell proliferation, invasion, migration and colony formation, but induces apoptosis and oxidative stress. Also, the expression of miRNA-21, miRNA-200a, miRNA-130a and mi-RNA-224 (which are indicators of poor prognosis of ovarian cancer) decreased significantly. Conclusion The potential of boric acid as a natural molecule may supports its effectiveness in reducing adverse effects arising from conventional ovarian cancer treatments.

Mounting evidence indicates the importance of microglia for proper brain development and function, as well as in complex stress-related neuropsychiatric disorders and cognitive decline along the aging trajectory. Considering that microglia are resident immune cells of the brain, a homeostatic maintenance of their effector functions that impact neuronal circuitry, such as phagocytosis and secretion of inflammatory factors, is critical to prevent the onset and progression of these pathological conditions. However, the molecular mechanisms by which microglial functions can be properly regulated under healthy and pathological conditions are still largely unknown. We aim to summarize recent progress regarding the effects of psychosocial stress and oxidative stress on microglial phenotypes, leading to neuroinflammation and impaired microglia-synapse interactions, notably through our own studies of inbred mouse strains, and most importantly, to discuss about promising therapeutic strategies that take advantage of microglial functions to tackle such brain disorders in the context of adult psychosocial stress or aging-induced oxidative stress. (c) 2017 Elsevier Inc. All rights reserved.

The herbicide paraquat (1,1'-dimethyl-4,4'-bipyridinium dichloride) has been banned in Europe since 2007 due to its high toxicity in humans. However, it is still widely used in Middle/ South America and in Asia where it is annually associated with a high incidence of unintentional and intentional poisoning. Human macrophage-like cell lines were used to shed more light on the inflammatory response elicited by paraquat. Paraquat (3-1000 mu M) reduced cell viability in a dose-and time-dependent manner. Exposure to 50 or 200 mu M paraquat for 24 h elevated the release of interleukin 8 and gene expression of tumor necrosis factor-alpha. Expression of the 11 beta-hydroxysteroid dehydrogenase 1 gene tended to increase, while cellular glutathione concentrations decreased. The anti-inflammatory effect of cortisol was significantly disrupted. The paraquat-induced cortisol resistance could not be prevented by N-acetyl-L-cysteine. However, a polyphenolic extract of grape seeds consisting of monomeric and oligomeric flavan-3-ols (MOF) reduced paraquat-induced inflammation in the presence of cortisol to baseline. In conclusion, the results suggest that an impaired cortisol response may contribute to paraquat-mediated inflammation. Agents with pleiotropic cellular and subcellular effects on redox regulation and inflammation, such as plant-derived polyphenols, may be an effective add-on to the therapy of paraquat intoxications with glucocorticoids.

There is evidence that pathogenic bacteria can adapt to antiseptics upon repeated exposure. More alarming is the concomitant increase in antibiotic resistance that has been described for some pathogens. Unfortunately, effects of adaptation and cross-adaptation are hardly known for oral pathogens, which are very frequently exposed to antiseptics. Therefore, this study aimed to determine the in vitro increase in minimum inhibitory concentrations (MICs) in oral pathogens after repeated exposure to chlorhexidine or cetylpyridinium chloride, to examine if (cross-)adaptation to antiseptics/antibiotics occurs, if (cross-)adaptation is reversible and what the potential underlying mechanisms are. When the pathogens were exposed to antiseptics, their MICs significantly increased. This increase was in general at least partially conserved after regrowth without antiseptics. Some of the adapted species also showed cross-adaptation, as shown by increased MICs of antibiotics and the other antiseptic. In most antiseptic-adapted bacteria, cell-surface hydrophobicity was increased and mass-spectrometry analysis revealed changes in expression of proteins involved in a wide range of functional domains. These in vitro data shows the adaptation and cross-adaptation of oral pathogens to antiseptics and antibiotics. This was related to changes in cell surface hydrophobicity and in expression of proteins involved in membrane transport, virulence, oxidative stress protection and metabolism.

Oxidative stress has been considered as the main mediator in neurodegenerative diseases. A high-fat diet (HFD) and metabolic diseases result in oxidative stress generation, leading to various neurodegenerative diseases via molecular mechanisms that remain largely unknown. Protein kinases play an important role in the homeostasis between cell survival and cell apoptosis. The mammalian sterile 20-like kinase-1 (MST1) protein kinase plays an important role in cellular apoptosis in different organ systems, including the central nervous system. In this study, we evaluated the MST1/c-Jun N-terminal kinase (JNK) dependent oxidative damage mediated cognitive dysfunction in HFD-fed mice and stress-induced hippocampal HT22 (mice hippocampal) cells. Our Western blot and immunofluorescence results indicate that HFD and stress-induced hippocampal HT22 cells activate MST1/JNK/Caspase-3 (Casp-3) signaling, which regulates neuronal cell apoptosis and beta-amyloid-cleaving enzyme (BACE1) expression and leads to impaired cognition. Moreover, MST1 expression inhibition by shRNA significantly reduced JNK/Casp-3 signaling. Our in vivo and in vitro experiments mimicking metabolic stress, such as a high-fat diet, hyperglycemia, and an inflammatory response, determined that MST1 plays a key regulatory role in neuronal cell death and cognition, suggesting that MST1 could be a potential therapeutic target for numerous neurodegenerative diseases.

Endothelial cell (EC) metabolism is important for health and disease. Metabolic pathways, such as glycolysis, fatty acid oxidation, and amino acid metabolism, determine vasculature formation. These metabolic pathways have different roles in securing the production of energy and biomass and the maintenance of redox homeostasis in vascular migratory tip cells, proliferating stalk cells, and quiescent phalanx cells, respectively. Emerging evidence demonstrates that perturbation of EC metabolism results in EC dysfunction and vascular pathologies. Here, we summarize recent insights into EC metabolic pathways and their deregulation in vascular diseases. We further discuss the therapeutic implications of targeting EC metabolism in various pathologies. ispartof: ANNUAL REVIEW OF PHYSIOLOGY, VOL 81 vol:81 pages:483-503 ispartof: location:United States status: published

In the normal central nervous system, endothelin-1 (ET-1) is found in some types of neurons, epithelial cells of the choroid plexus, and endothelial cells of microvessels, but it is usually not detectable in glial cells. However, in different pathological conditions, astrocytes adapting a reactive phenotype express high levels of ET-1 and its receptors, mainly the ETB receptor. ET-1 released by reactive astrocytes appears mainly to have neurodeleterious effects by mechanisms that include constriction of cerebral arterioles leading to impairment of the cerebral microcirculation, increase of blood brain barrier permeability, inflammation, excitotoxicity, impairment of fast axonal transport, and astrogliosis. A few studies in rodents found that ET-1 increased the astrocytic expression of brain-derived neurotrophic factor, glial cell-line derived neurotrophic factor and neurotropin-3, and the production of endocannabinoids. However, whether this occurs in physiological or pathological conditions is unclear. This review summarizes current knowledge about the role of the astrocytic ET-1 system in acute and chronic neurological conditions, including multiple sclerosis, ischemic stroke and hypoxic/ischemic brain injury, traumatic brain injury, subarachnoid hemorrhage, Alzheimer's disease, Binswanger's disease and post stroke dementia, amyotrophic lateral sclerosis, and CNS infections. Counteracting the harmful effects of astrocytic ET-1 may represent a promising therapeutic target for mitigating secondary brain damage in a variety of neurological diseases. We also briefly address the role of astrocytic ET-1 in astrocytic tumors and pain. (C) 2016 Elsevier Ltd. All rights reserved.

Bu çalışma, Bursa Uludağ Üniversitesi Fen Bilimleri Enstitüsünde Hülya Arslan'in danışmanlığında Ayşegül Akpınar tarafından yazılan "Ağır metal stresi koşullarında Verbascum olympicum Boiss. türünün enzimatik aktivitesi üzerinde araştırmalar" adlı doktora tezine dayanılarak hazırlanmıştır. The endemic Verbascum olympicum has characteristics that allows it to live in degraded areas of Uludag Mountain, Turkey and therefore known as a ruderal species. In this study, V. olympicum seeds collected from Uludag Mountain were grown in the Hoagland nutrient solution, under hydroponic conditions. The activity of antioxidative enzymes (superoxide dismutase, SOD; catalase, CAT; ascorbate peroxidase, APX) were examined to demonstrate the role of antioxidative mechanism in the seedlings exposed to different Cu concentrations (0, 50, 250, 500 mu M) for seven days. Also, certain growth parameters (such as the water content, biomass production, soluble protein), the level of lipid peroxidation, cell membrane injury and permeability were investigated. As a result, some toxic effects are observed following the application of 500 mu M Cu, after the seedlings growing in 50 and 250 mM Cu concentrations showed high resistance and survived in hydroponic conditions. Our findings provide information about the resistance of V. olympicum seedlings to oxidative stress caused by excessive Cu concentrations.

Oxidative stress occurs when there is an imbalance between the production of reactive oxygen species (ROS) and antioxidant defense. Exposure to pollutants may increase ROS and affect antioxidant levels, and the resulting oxidative stress may negatively affect both reproduction and survival. We measured concentrations of 18 persistent organic pollutants (POPs) and 9 toxic elements in blood, as well as total antioxidant capacity (TAC), total glutathione (tGSH), and carotenoids in plasma of Baltic and Arctic female common eiders (Somateria mollissima) (N = 54) at the end of their incubation-related fasting. The more polluted Baltic population had higher TAC and tGSH concentrations compared to the Arctic population. Carotenoid levels did not differ between populations. The effect of mixtures of pollutants on the antioxidants was assessed, and the summed molar blood concentrations of 14 POPs were positively related to TAC. There was no significant relationship between the analyzed pollutants and tGSH concentrations. The adaptive improvement of the antioxidant defense system in the Baltic population may be a consequence of increased oxidative stress. However, both increased oxidative stress and energy allocation toward antioxidant defense may have adverse consequences for Baltic eiders at the incubation stage, when energy resources reach an annual minimum due to incubation-related fasting.

Yahyazadeh, Ahmad/0000-0002-6093-3588 WOS: 000407627200006 PubMed: 28598684 We examined the possible effects of elemental mercury vapor on the liver of the female rats. We divided the animals into an untreated control group and an experimental group that was exposed to mercury vapor for 45 days. Liver samples were obtained for histological and stereological analysis. The total liver, parenchyma and sinusoid volumes were increased significantly in the mercury vapor treated group compared to controls. Also, the mean density, total number and mean nuclear diameter of hepatocytes, except for binucleated hepatocytes, was decreased in the experimental group compared to controls. Light and electron microscopy revealed alterations of liver structure of the experimental animals compared to controls.

In agriculture, heavy metal contamination of soil interferes with processes associated with plant growth, development and productivity. Here, we describe oxidative and redox changes, and deleterious injury within cotyledons and seedlings caused by exposure of germinating (Phaseolus vulgaris L. var. soisson nain hatif) seeds to copper (Cu). Cu induced a marked delay in seedling growth, and was associated with biochemical disturbances in terms of intracellular oxidative status, redox regulation and energy metabolism. In response to these alterations, modulation of activities of antioxidant proteins (thioredoxin and glutathione reductase, peroxiredoxin) occurred, thus preventing oxidative damage. In addition, oxidative modification of proteins was detected in both cotyledons and seedlings by one- and two-dimensional electrophoresis. These modified proteins may play roles in redox buffering. The changes in activities of redox proteins underline their fundamental roles in controlling redox homeostasis. However, observed differential redox responses in cotyledon and seedling tissues showed a major capacity of the seedlings' redox systems to protect the reduced status of protein thiols, thus suggesting quantitatively greater antioxidant protection of proteins in seedlings compared to cotyledon. To our knowledge, this is the first comprehensive redox biology investigation of the effect of Cu on seed germination.

A wide variety of natural sources are under investigation to evaluate their possible use for new functional ingredient formulation. Some records attested the traditional and ancient use of wild harvested microalgae as human food but their cultivation for different purposes started about 40 years ago. The most popular species are Arthrospira (traditional name, Spirulina), Chlorella spp., Dunaliella spp. and Haematococcus spp. Microalgae provide a bewildering array of opportunities to develop healthier food products using innovative approaches and a number of different strategies. Compared to other natural sources of bioactive ingredients, microalgae have many advantages such as their huge biodiversity, the possibility to grow in arid land and with limited fresh water consumption and the flexibility of their metabolism, which could be adapted to produce specific molecules. All these factors led to very sustainable production making microalgae eligible as one of the most promising foods for the future, particularly as source of proteins, lipids and phytochemicals. In this work, a revision of the knowledge about the use of microalgae as food and as a source of functional ingredients has been performed. The most interesting results in the field are presented and commented upon, focusing on the different species of microalgae and the activity of the nutritionally relevant compounds. A summary of the health effects obtained together with pros and cons in the adoption of this natural source as functional food ingredients is also proposed. © the Partner Organisations 2014.

In the normal central nervous system, endothelin-1 (ET-1) is found in some types of neurons, epithelial cells of the choroid plexus, and endothelial cells of microvessels, but it is usually not detectable in glial cells. However, in different pathological conditions, astrocytes adapting a reactive phenotype express high levels of ET-1 and its receptors, mainly the ETB receptor. ET-1 released by reactive astrocytes appears mainly to have neurodeleterious effects by mechanisms that include constriction of cerebral arterioles leading to impairment of the cerebral microcirculation, increase of blood brain barrier permeability, inflammation, excitotoxicity, impairment of fast axonal transport, and astrogliosis. A few studies in rodents found that ET-1 increased the astrocytic expression of brain-derived neurotrophic factor, glial cell-line derived neurotrophic factor and neurotropin-3, and the production of endocannabinoids. However, whether this occurs in physiological or pathological conditions is unclear. This review summarizes current knowledge about the role of the astrocytic ET-1 system in acute and chronic neurological conditions, including multiple sclerosis, ischemic stroke and hypoxic/ischemic brain injury, traumatic brain injury, subarachnoid hemorrhage, Alzheimer's disease, Binswanger's disease and post stroke dementia, amyotrophic lateral sclerosis, and CNS infections. Counteracting the harmful effects of astrocytic ET-1 may represent a promising therapeutic target for mitigating secondary brain damage in a variety of neurological diseases. We also briefly address the role of astrocytic ET-1 in astrocytic tumors and pain. (C) 2016 Elsevier Ltd. All rights reserved.

Mitochondrial impairment induced by oxidative stress is a main characteristic of intrinsic cell death pathways in neurons underlying the pathology of neurodegenerative diseases. Therefore, protection of mitochondrial integrity and function is emerging as a promising strategy to prevent neuronal damage. Here, we show that pharmacological inhibition of hypoxia-inducible factor prolyl-4-hydroxylases (HIF-PHDs) by adaptaquin inhibits lipid peroxidation and fully maintains mitochondrial function as indicated by restored mitochondrial membrane potential and ATP production, reduced formation of mitochondrial reactive oxygen species (ROS) and preserved mitochondrial respiration, thereby protecting neuronal HT-22 cells in a model of glutamate-induced oxytosis. Selective reduction of PHD1 protein using CRISPR/Cas9 technology also reduced both lipid peroxidation and mitochondrial impairment, and attenuated glutamate toxicity in the HT-22 cells. Regulation of activating transcription factor 4 (ATF4) expression levels and related target genes may mediate these beneficial effects. Overall, these results expose HIF-PHDs as promising targets to protect mitochondria and, thereby, neurons from oxidative cell death.

With many metal-based drugs extensively used today in the treatment of cancer, attention has focused on the development of new coordination compounds with antitumor activity with europium(III) complexes recently introduced as novel anticancer drugs. The aim of this work is to design new Eu(III) complexes with gallic acid, an antioxida'nt phenolic compound. Gallic acid was chosen because it shows anticancer activity without harming health cells. As antioxidant, it helps to protect human cells against oxidative damage that implicated in DNA damage, cancer, and accelerated cell aging. In this work, the formation of binary and ternary complexes of Eu(III) with gallic acid, primary ligand, and amino acids alanine, leucine, isoleucine, and tryptophan was studied by glass electrode potentiometry in aqueous solution containing 0.1 M NaNO3 at (298.2 +/- 0.1) K. Their overall stability constants were evaluated and the concentration distributions of the complex species in solution were calculated. The protonation constants of gallic acid and amino acids were also determined at our experimental conditions and compared with those predicted by using conductor-like screening model for realistic solvation (COSMO-RS) model. The geometries of Eu(III)-gallic acid complexes were characterized by the density functional theory (DFT). The spectroscopic UV-visible and photoluminescence measurements are carried out to confirm the formation of Eu(III)-gallic acid complexes in aqueous solutions. (C) 2016 Elsevier Inc. All rights reserved.

In this study, one-year-old shoots of the olive (Olea europaea L.) cv. Gemlik were tested at artificial low temperatures (4, -5A degrees C, -10A degrees C, and -20A degrees C) every month for two years. For low temperature treatment, the degree of cell membrane injury in leaves and barks was determined by ion leakage method. In addition, with regard to antioxidative defense mechanism, activities of catalase (CAT, EC 1.11.1.6) and ascorbate peroxidase (APX, EC 1.11.1.11) enzymes were determined. Leaf and bark tissues subjected to 4A degrees C and -5A degrees C injured to a limited extent in all months. However, more than 50% injury occurred by temperatures equal to or colder than -10A degrees C treatments depending on the season. For -10A degrees C and -20A degrees C treatments, the lowest and the highest injury in leaf and bark tissues were detected during winter and summer seasons, respectively. We determined in this study that CAT and APX enzyme activities are generally higher during fall and winter compared with those in summer. On the other hand, CAT and APX enzyme activities started increasing during fall along with a decreasing freezing injury while the activities of these enzymes decreased to some extent during winter when freezing injury was the lowest. In addition, while CAT activity decreased with low temperature treatments, APX activity did not change until -5A degrees C treatment but decreased with decreasing temperatures starting from -10A degrees C depending on the month the tissue was obtained. In conclusion, olive plant shows considerable tolerance to low temperatures that are achieved after daily gradual decreases by increasing cell membrane stability through complicated mechanisms including antioxidative enzyme metabolisms. In addition, APX may be more effective in maintaining cold-hardiness of olive compared with CAT. Türkiye Cumhuriyeti Devlet Planlama Teşkilatı

For some cancer survivors chemotherapy treatment is associated with lasting cognitive impairment, long after treatment cessation. Several candidate mechanisms have been suggested, yet clinical research has been unable to clearly tease apart these hypotheses. Rodent research has allowed a systematic study of these underlying mechanisms in the absence of potential patient confounds. Herein, this research is reviewed with emphasis on the role of the blood-brain barrier, neurogenesis, oxidative stress, white matter, immune system/(neuro) inflammation, HPA axis, blood flow, and cancer in chemotherapy-induced cognitive impairment. Furthermore, potential pharmacotherapy and behavioral intervention strategies are reviewed. This paper ends with methodological considerations in study of chemotherapy and cognition. (C) 2010 Elsevier Ltd. All rights reserved.

For some cancer survivors chemotherapy treatment is associated with lasting cognitive impairment, long after treatment cessation. Several candidate mechanisms have been suggested, yet clinical research has been unable to clearly tease apart these hypotheses. Rodent research has allowed a systematic study of these underlying mechanisms in the absence of potential patient confounds. Herein, this research is reviewed with emphasis on the role of the blood-brain barrier, neurogenesis, oxidative stress, white matter, immune system/(neuro) inflammation, HPA axis, blood flow, and cancer in chemotherapy-induced cognitive impairment. Furthermore, potential pharmacotherapy and behavioral intervention strategies are reviewed. This paper ends with methodological considerations in study of chemotherapy and cognition. (C) 2010 Elsevier Ltd. All rights reserved.

Background/aim: In the present study, the protective effect of erdosteine against cyclosporine-induced injury in rat liver was investigated with histological and biochemical methods. Materials and methods: Thirty-two Wistar albino male rats were randomly divided into 4 groups: control (n = 8), cyclosporine (n = 8, 20 mg kg(-1) day(-1) i.p.), cyclosporine + erdosteine (n = 8, erdosteine 12 mg kg(-1) day(-1) orally), and erdosteine (n = 8). At the end of day 12, liver tissues were removed for histological and biochemical analysis. After liver tissues were fixed in 10% buffered neutral formalin, routine histological processes were applied and tissue sections were stained with hematoxylin and eosin, periodic acid-Schiff, and elastic fiber stain methods. One hundred lobules of liver were examined for each group and evaluated statistically. The levels of malondialdehyde and glutathione peroxidase, as well as the activities of superoxide dismutase, were determined. Results: The cyclosporine group showed significant histopathological changes compared to the control. In the cyclosporine + erdosteine group, histopathological changes of hepatic damage were markedly reduced. Histological findings were supported by biochemical results. Conclusion: Erdosteine could attenuate cyclosporine-induced liver injury.

Pest. Biochem. Physiol.ISI Document Delivery No.: CU2NCTimes Cited: 0Cited Reference Count: 23Goujon, Eric Richard, Claire Goupil, Pascale Ledoigt, GerardEurope (FEDER); Auvergne Regional Council (CPER)This work was supported by grants from Europe (FEDER) and Auvergne Regional Council (CPER 2007-2013). We thank Celine Sac, Dominique Marcon and Margot Stawinoga for their skillful assistance.Academic press inc elsevier scienceSan diego; The cytotoxic effects of 2-chloro-4-mesylbenzoic acid (CMBA) and xanthene-1,9-dione-3,4-dihydro-6-methylsulphonyl (XDD), the two main photoproducts of sulcotrione, were investigated on Allium root meristematic cells at different concentrations. Degradation of sulcotrione was correlated to mitotic index decrease, together with increasing anomaly and c-mitosis frequencies. Mitotic index significantly decreased with increasing XDD and CMBA concentrations. Cell frequency with abnormal chromosomes increased with CMBA or XDD application rates. In contrast, CMBA induced a low micronucleus rate even for high concentrations while XDD increased the micronucleus ratio. C-mitoses, chromosomal aberrations due to an inactivation of the spindle, were enhanced by CMBA treatments but not by XDD. The photochemical degradation process of the pesticide can change the risk for the environment. (C) 2015 Elsevier Inc. All rights reserved.

Excess use of alcohol is known to be associated with liver diseases such as fatty liver, alcoholic hepatitis, and cirrhosis. Various practices may be applied to prevent or treat the damage caused by chronic alcoholism. Coprinus comatus (O.F. Müll.) Pers. (Agaricaceae) is a macrofungus that has been reported to aid the recovery of murine livers damaged by benzopyrene.In this study, the possible therapeutic effects of three different doses (50, 100, and 150 mg/kg) of C. comatus polysaccharide (PS) extract were studied in rats subjected to an alcoholic diet. The histological and biochemical results were compared between the control and experimental groups.Modified Lieber-Decarli's calorie-adjusted liquid alcohol diet was given orally for 60 d. In addition to histopathology, alanine transaminase (ALT), aspartate transaminase (AST), mitochondrial membrane integrity, total cytochrome-c oxidase activity (TotalStCox), total mitochondrial cytochrome-c oxidase activity (TotalMtStCox), and caspase-3 values were used as liver parameters, and liver sections from all experimental groups were examined by electron microscopy.Using histopathological assessment, it was observed that there was a decline in liver hepatocyte vacuolization in the treatment group fed 50 mg PS/kg. The TotalStCox and TotalMtStCox values of this group differed from the EtOH control group (p 0.05).Daily administration of 50 mg/kg of C. comatus PS extract considerably reduced the negative effects of alcohol on liver structure and function.

Plants play important roles in human life not only as suppliers of oxygen but also as a fundamental resource to sustain the human race on this earthly plane. Plants also play a major role in our nutrition by converting energy from the sun during photosynthesis. In addition, plants have been used extensively in traditional medicine since time immemorial. Information in the biomedical literature has indicated that many natural herbs have been investigated for their efficacy against lethal irradiation. Pharmacological studies by various groups of investigators have shown that natural herbs possess significant radioprotective activity. In view of the immense medicinal importance of natural product based radioprotective agents, this review aims at compiling all currently available information on radioprotective agents from medicinal plants and herbs, especially the evaluation methods and mechanisms of action. In this review we particularly emphasize on ethnomedicinal uses, botany, phytochemistry, mechanisms of action and toxicology. We also describe modern techniques for evaluating herbal samples as radioprotective agents. The usage of herbal remedies for combating lethal irradiation is a green antiirradiation approach for the betterment of human beings without high cost, side effects and toxicity.